A targeting construct containing the neomycin and HSTK genes and 10 kb of genomic homology has been constructed to disrupt the Muc5ac gene. The construct has been electroporated into mouse ES cells but to date only 2 PCR positive clones of about 1,000 analyzed have been obtained. These clones are being further analyzed by PCR and genomic Southern analysis to verify targeting. Once targeting is confirmed these clones will be injected into mouse blastocyst to generate chimeras and achieve germline transmission.